Pyrroloquinoline quinone (hereinafter referred to as “PQQ”) was discovered in 1979 as a coenzyme of methanol dehydrogenase in methanol assimilating microorganisms (see “Nature,” 1979, Vol. 280, pp. 843-844; and “FEBS Letters,” 1979, Vol. 108, pp. 443-446). Other than such microorganisms, PQQ has also been detected in edible plants such as soybean, horse bean, green pepper, potato, parsley, and spinach and processed foods such as vinegar, tea, cocoa, natto, and tofu (see “Biochemical Journal,” 1995, Vol. 307, pp. 331-333). Furthermore, the presence of PQQ in humans and rats in vivo has been reported (see “Biochimica et Biophysica Acta,” 1992, Vol. 1156, pp. 62-66). PQQ is a highly safe substance.
Known effects of PQQ are as follows: a cell growth promoting effect (see JP Patent Publication (Kokai) No. 61-58584 A (1986)), an active oxygen eliminating effect (see JP Patent Publication (Kokai) No. 5-078247 A (1993)), an aldose reductase-inhibiting effect (see JP Patent Publication (Kokai) No. 6-256191 A (1994)), a nerve growth factor production promoting effect (see JP Patent Publication (Kokai) No. 6-211660 A (1994)), a reverse transcriptase inhibiting effect (see JP Patent Publication (Kokoku) No. 8-005792 B (1996)), an anti-cataract effect (see JP Patent Publication (Kokoku) No. 8-005791 B (1996)), melanin production suppressing and skin lightening effects (see JP Patent Publication (Kokai) No. 8-020512 A (1996)), and an ultraviolet absorption effect (see JP Patent No. 3625493), for example.
Meanwhile, medicaments for improvement of insulin resistance are thought to be useful as prophylactic and therapeutic drugs for lifestyle-related diseases such as diabetes, arteriosclerosis, and hyperlipemia. In particular, type II diabetes is a disease that is developed mainly due to lowered insulin action (insulin resistance) in target tissues of insulin, including skeletal muscle, liver, and adipose tissue. The insulin resistance improving agent is effective as a therapeutic drug for such type II diabetes. Based on their mechanisms of action, therapeutic agents for diabetes are classified as sulfonylurea agents, prompt and short acting agents for accelerating insulin secretion, α-glucosidase inhibitors, biguanides, or thiazolidin derivatives. These therapeutic agents are used independently or in combinations for the treatment of diabetes. Of these therapeutic agents, thiazolidine-based therapeutic agents, which are general insulin resistance improving agents, are known to cause body weight gain as a side effect (see “American Journal Physiology Endocrinology Metabolism” 2003, Vol. 284, pp. 966-971). Therefore, it has been desired to develop an insulin resistance improving agent that would have mild side effects and would be highly safe.